Interferons (IFN-alpha, IFN-beta, and IFN-gamma) are natural host proteins which have antiviral, immunoregulatory, and antiproliferative activities. A number of clinical trials have examined interferons for their clinical potential. Unfortunately, while they have shown real promise for the control of certain types of cancer, they have been limited in their effectiveness and have not been found to be highly potent against most of the types of cancers tested. Further, interferon therapy has a number of side effects, including bone marrow suppression. A major challenge is to increase the antitumor activity of the interferons while reducing or moderating their side effects. This proposal focuses on this challenge by 1) evaluating combined interferon treatment (IFN-gamma plus either IFN-alpha or IFN-beta) in various treatment protocols as a means of maximizing interferon activity; 2) evaluating the combined effects of colony stimulating factors and other myeloregulatory agents as a means of minimizing the bone marrow suppressive effect of interferon therapy; 3) removing an inhibitor of interferon action from IFN- gamma preparations as a means of maximizing IFN-gamma activity; and, 4) evaluating the combined effects of antitumor drugs and interferons as a means of maximizing their antitumor activities. The proposed research seeks to investigate basic mechanisms, while providing important insights for the clinical application of interferon.